3pq1

Structural highlights

Disease

[PAPD1_HUMAN] Autosomal recessive spastic ataxia - optic atrophy - dysarthria. The disease is caused by mutations affecting the gene represented in this entry. MTPAP mutations result in a defect of mitochondrial mRNA maturation. Affected individuals exhibit a drastic decrease in poly(A) tail length of mitochondrial mRNA transcripts, including COX1 and RNA14 (PubMed:20970105).^[1]

Function

[PAPD1_HUMAN] Polymerase that creates the 3' poly(A) tail of mitochondrial transcripts. Can use all four nucleotides, but has higher activity with ATP and UTP (in vitro). Plays a role in replication-dependent histone mRNA degradation. May be involved in the terminal uridylation of mature histone mRNAs before their degradation is initiated. Might be responsible for the creation of some UAA stop codons which are not encoded in mtDNA.^{[2] [3] [4] [5] [6]}

See Also

• Poly(A) Polymerase
• RNA polymerase
• RNA uridylyltransferase

References

1. ↑ Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K, Patton MA, Sharifi R, Harlalka G, Simpson MA, Dick K, Reed JA, Al-Memar A, Chrzanowska-Lightowlers ZM, Cross HE, Lightowlers RN. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet. 2010 Nov 12;87(5):655-60. doi: 10.1016/j.ajhg.2010.09.013. Epub, 2010 Oct 21. PMID:20970105 doi:http://dx.doi.org/10.1016/j.ajhg.2010.09.013
2. ↑ Tomecki R, Dmochowska A, Gewartowski K, Dziembowski A, Stepien PP. Identification of a novel human nuclear-encoded mitochondrial poly(A) polymerase. Nucleic Acids Res. 2004 Nov 16;32(20):6001-14. Print 2004. PMID:15547249 doi:http://dx.doi.org/32/20/6001
3. ↑ Nagaike T, Suzuki T, Katoh T, Ueda T. Human mitochondrial mRNAs are stabilized with polyadenylation regulated by mitochondria-specific poly(A) polymerase and polynucleotide phosphorylase. J Biol Chem. 2005 May 20;280(20):19721-7. Epub 2005 Mar 14. PMID:15769737 doi:http://dx.doi.org/10.1074/jbc.M500804200
4. ↑ Mullen TE, Marzluff WF. Degradation of histone mRNA requires oligouridylation followed by decapping and simultaneous degradation of the mRNA both 5' to 3' and 3' to 5'. Genes Dev. 2008 Jan 1;22(1):50-65. doi: 10.1101/gad.1622708. PMID:18172165 doi:10.1101/gad.1622708
5. ↑ Crosby AH, Patel H, Chioza BA, Proukakis C, Gurtz K, Patton MA, Sharifi R, Harlalka G, Simpson MA, Dick K, Reed JA, Al-Memar A, Chrzanowska-Lightowlers ZM, Cross HE, Lightowlers RN. Defective mitochondrial mRNA maturation is associated with spastic ataxia. Am J Hum Genet. 2010 Nov 12;87(5):655-60. doi: 10.1016/j.ajhg.2010.09.013. Epub, 2010 Oct 21. PMID:20970105 doi:http://dx.doi.org/10.1016/j.ajhg.2010.09.013
6. ↑ Bai Y, Srivastava SK, Chang JH, Manley JL, Tong L. Structural basis for dimerization and activity of human PAPD1, a noncanonical poly(A) polymerase. Mol Cell. 2011 Feb 4;41(3):311-20. PMID:21292163 doi:10.1016/j.molcel.2011.01.013
7. ↑ Bai Y, Srivastava SK, Chang JH, Manley JL, Tong L. Structural basis for dimerization and activity of human PAPD1, a noncanonical poly(A) polymerase. Mol Cell. 2011 Feb 4;41(3):311-20. PMID:21292163 doi:10.1016/j.molcel.2011.01.013